Lack of correlation between the levels of soluble cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and the CT-60 genotypes

Sharad B Purohit, Robert Podolsky, Christin Collins, Weipeng Zheng, Desmond Schatz, Andy Muir, Diane Hopkins, Yi Hua Huang, Jin-Xiong She

Research output: Contribution to journalArticle

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Abstract

Background: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in downregulation of antigen-activated immune response and polymorphisms at the CTLA-4 gene have been shown to be associated with several autoimmune diseases including type-1 diabetes (T1D). The etiological mutation was mapped to the CT60-A/G single nucleotide polymorphism (SNP) that is believed to control the processing and production of soluble CTLA-4 (sCTLA-4). Methods: We therefore determined sCTLA-4 protein levels in the sera from 82 T1D patients and 19 autoantibody positive (AbP) subjects and 117 autoantibody negative (AbN) controls using ELISA. The CT-60 SNP was genotyped for these samples by using PCR and restriction enzyme digestion of a 268 bp DNA segment containing the SNP. Genotyping of CT-60 SNP was confirmed by dye terminating sequencing reaction. Results: Higher levels of sCTLA-4 were observed in T1D (2.24 ng/ml) and AbP (mean = 2.17 ng/ml) subjects compared to AbN controls (mean = 1.69 ng/ml) with the differences between these subjects becoming significant with age (p = 0.02). However, we found no correlation between sCTLA-4 levels and the CTLA-4 CT-60 SNP genotypes. Conclusion: Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 may be a risk factor for T1D. However, our results do not support the conclusion that the CT-60 SNP controls the expression of sCTLA-4.

Original languageEnglish (US)
Article number8
JournalJournal of Autoimmune Diseases
Volume2
DOIs
StatePublished - Oct 31 2005

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CTLA-4 Antigen
Single Nucleotide Polymorphism
Genotype
Type 1 Diabetes Mellitus
Autoantibodies
Autoimmune Diseases
Histocompatibility Antigens Class II
Serum
Digestion
Coloring Agents
Down-Regulation
Enzyme-Linked Immunosorbent Assay
Polymerase Chain Reaction
Mutation
DNA
Enzymes
Genes

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

Lack of correlation between the levels of soluble cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and the CT-60 genotypes. / Purohit, Sharad B; Podolsky, Robert; Collins, Christin; Zheng, Weipeng; Schatz, Desmond; Muir, Andy; Hopkins, Diane; Huang, Yi Hua; She, Jin-Xiong.

In: Journal of Autoimmune Diseases, Vol. 2, 8, 31.10.2005.

Research output: Contribution to journalArticle

Purohit, Sharad B ; Podolsky, Robert ; Collins, Christin ; Zheng, Weipeng ; Schatz, Desmond ; Muir, Andy ; Hopkins, Diane ; Huang, Yi Hua ; She, Jin-Xiong. / Lack of correlation between the levels of soluble cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and the CT-60 genotypes. In: Journal of Autoimmune Diseases. 2005 ; Vol. 2.
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